Tìm theo
Busulfan
Các tên gọi khác (16 ) :
  • 1,4-Bis(methanesulfonoxy)butane
  • 1,4-Butanediol dimethanesulfonate
  • 1,4-Dimesyloxybutane
  • 1,4-Dimethanesulfonoxybutane
  • Bisulfex
  • Busulfan
  • Busulfano
  • Busulfanum
  • Leucosulfan
  • Mablin
  • Mielucin
  • Misulban
  • Mitostan
  • Myeloleukon
  • Myleran
  • Tetramethylene bis(methanesulfonate)
Thuốc giảm miễn dịch
Thuốc Gốc
Small Molecule
CAS: 55-98-1
ATC: L01AB01
ĐG : GlaxoSmithKline Inc. , http://www.gsk.com
CTHH: C6H14O6S2
PTK: 246.302
Busulfan is a bifunctional alkylating agent, having a selective immunosuppressive effect on bone marrow. It is not a structural analog of the nitrogen mustards. It has been used in the palliative treatment of chronic myeloid leukemia (myeloid leukemia, chronic), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C6H14O6S2
Phân tử khối
246.302
Monoisotopic mass
246.02317956
InChI
InChI=1S/C6H14O6S2/c1-13(7,8)11-5-3-4-6-12-14(2,9)10/h3-6H2,1-2H3
InChI Key
InChIKey=COVZYZSDYWQREU-UHFFFAOYSA-N
IUPAC Name
4-(methanesulfonyloxy)butyl methanesulfonate
Traditional IUPAC Name
busulfan
SMILES
CS(=O)(=O)OCCCCOS(C)(=O)=O
Độ tan chảy
106-107
Độ hòa tan
6.9E+004 mg/L
logP
-0.52
logS
-1.7
PSA
86.74 Å2
Refractivity
49.57 m3·mol-1
Polarizability
23.64 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
4
H Bond Donor Count
0
Physiological Charge
0
Number of Rings
0
Bioavailability
1
Rule of Five
true
Dược Lực Học : Busulfan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn leads to a miscoding of DNA. Alkylating agents are cell cycle-nonspecific and work by three different mechanisms, all of which achieve the same end result - disruption of DNA function and cell death. Overexpression of MGST2, a glutathione s-transferase, is thought to confer resistance to busulfan. The role of MGST2 in the metabolism of busulfan is unknown however.
Cơ Chế Tác Dụng : Busulfan is a bifunctional alkylating agent, having a selective immunosuppressive effect on bone marrow. It is not a structural analog of the nitrogen mustards. It has been used in the palliative treatment of chronic myeloid leukemia (myeloid leukemia, chronic), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen. [PubChem] Busulfan is an alkylating agent that contains 2 labile methanesulfonate groups attached to opposite ends of a 4-carbon alkyl chain. Once busulfan is hydrolyzed, the methanesulfonate groups are released and carbonium ions are produced. These carbonium ions alkylate DNA, which results in the interference of DNA replication and RNA transcription, ultimately leading to the disruption of nucleic acid function. Specifically, its mechanism of action through alkylation produces guanine-adenine intrastrand crosslinks. This occurs through an SN2 reaction in which the relatively nucleophilic guanine N7 attacks the carbon adjacent to the mesylate leaving group. This kind of damage cannot be repaired by cellular machinery and thus the cell undergoes apoptosis.
Dược Động Học :
▧ Absorption :
Completely absorbed from the gastrointestinal tract. Busulfan is a small, highly lipophilic molecule that crosses the blood-brain-barrier. The absolute bioavailability, if a single 2 mg IV bolus injection is given to adult patients, is 80% ± 20%. In children (1.5 - 6 years old), the absolute bioavailability was 68% ± 31%. When a single oral dose is given to patients, the area under the curve (AUC) was 130 ng•hr/mL. The peak plasma concentration when given orally is 30 ng/mL (after dose normalization to 2 mg). It takes 0.9 hours to reach peak plasma concentration after dose normalization to 4 mg.
▧ Protein binding :
32% bound to plasma proteins and 47% bound to red blood cells.
▧ Metabolism :
Busulfan is extensively metabolizes in the hepatic. Busulfan is predominantly metabolized by conjugation with glutathione, both spontaneously and by glutathione S-transferase (GST) catalysis. GSTA1 is the primary GST isoform that facilitates the the metabolism of busulfan. Other GST isoforms that are also involved are GSTM1 and GSTP1. At least 12 metabolites have been identified among which tetrahydrothiophene, tetrahydrothiophene 12-oxide, sulfolane, and 3-hydroxysulfolane were identified. These metabolites do not have cytotoxic activity.
▧ Route of Elimination :
Following administration of 14C- labeled busulfan to humans, approximately 30% of the radioactivity was excreted into the urine over 48 hours; negligible amounts were recovered in feces. Less than 2% of the administered dose is excreted in the urine unchanged within 24 hours. Elimination of busulfan is independent of renal function.
▧ Half Life :
2.6 hours
▧ Clearance :
* 2.52 ml/min/kg [Following an infusion of dose of 0.8 mg/kg every six hours, for a total of 16 doses over four days]
Độc Tính : Signs of overdose include allergic reaction, unusual bleeding or bruising, sudden weakness or unusual fatigue, persistent cough, congestion, or shortness of breath; flank, stomach or joint pain; pronounced nausea, vomiting, diarrhea, dizziness, confusion, or darkening of the skin, chills, fever, collapse, and loss of consciousness.
Chỉ Định : For use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous (myeloid, myelocytic, granulocytic) leukemia (FDA has designated busulfan as an orphan drug for this use). It is also used as a component of pretransplant conditioning regimens in patients undergoing bone marrow transplantation for acute myeloid leukemia and nonmalignant diseases.
Tương Tác Thuốc :
  • Bendamustine Increases toxicity through pharmacodynamic synergism.
  • Itraconazole Itraconazole reduced busulfan clearance by up to 25% in patients receiving itraconazole compared to those that did not receive it. Concomitant therapy may lead to toxic plasma levels of busulfan.
  • Metronidazole Metronidazole increases the effect/toxicity of busulfan
  • Telithromycin Telithromycin may reduce clearance of Busulfan. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Busulfan if Telithromycin is initiated, discontinued or dose changed.
  • Tioguanine Busulfan increases the hepatoxicity of Thioguanine during long-term concomitant therapy.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of busulfan by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of busulfan if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Injection, solution - Intravenous - 6 mg/mL
Tablet - Oral - 2 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Myleran 2 mg tablet
    Giá bán buôn : USD >4.55
    Đơn vị tính : tablet
  • Biệt dược thương mại : Busulfex 6 mg/ml vial
    Giá bán buôn : USD >115.08
    Đơn vị tính : ml
Nhà Sản Xuất
  • Công ty : Pierre Fabre
    Sản phẩm biệt dược : Busilvex
  • Công ty : PDL
    Sản phẩm biệt dược : Busulfex
  • Công ty : HAC Pharma
    Sản phẩm biệt dược : Myléran
  • Công ty : GlaxoSmithKline
    Sản phẩm biệt dược : Myleran
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01008
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2478
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506234
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00248
ChemSpider
http://www.chemspider.com/Chemical-Structure.2384.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/67286-0054-2
PharmGKB
http://www.pharmgkb.org/drug/PA448691
Wikipedia
http://en.wikipedia.org/wiki/Busulfan
RxList
http://www.rxlist.com/cgi/generic2/busulfan.htm
Drugs.com
http://www.drugs.com/cdi/busulfan.html
... loading
... loading